Casticin inhibits human prostate cancer DU 145 cell migration and invasion via Ras/Akt/NF-κB signaling pathways
Casticin inhibits human prostate cancer DU 145 cell migration and invasion via Ras/Akt/NF-κB signaling pathways
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DOI：
10.1111/jfbc.12902
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发表时间：
2019-07-01
影响因子：
4
通讯作者：
Chung, Jing-Gung
中科院分区：
文献类型：
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作者：
Lin, Chia-Chang;Chen, Kuen-Bao;Chung, Jing-Gung
紫花牡荆素是一种来源于天然植物的多甲氧基黄酮，具有诱导细胞凋亡等生物活性。在这项研究中，我们展示了牡荆苷对抑制前列腺癌细胞转移的有益作用。紫花苜蓿素减少总活细胞数，因此，我们选择低剂量的紫花苜蓿素用于以下实验。紫花苜蓿素降低细胞迁移率，抑制细胞迁移和侵袭，并降低MMP-2/-9的细胞明胶分解活性。此外，在24和48小时处理时，紫花苜蓿素抑制AKT、GSK 3 α β、Snail和MMP（MMP-2、MMP-9、MMP-13和MMP-7）的蛋白水平。紫花苜蓿素仅在处理48小时时降低NF-κ B B p65、GRB 2、SOS-1、MEK、p-ERK 1/2和p-JNK 1/2的表达。然而，紫花苜蓿素在治疗24小时降低E-钙粘蛋白的水平，但在48小时升高。新的研究结果表明，紫花苜蓿素可能代表一个新的和有前途的治疗剂的转移性前列腺癌。实际应用从天然植物中提取的紫花苜蓿素作为中药在中国人中使用已有数千年的历史。在本研究中，紫花苜蓿素减弱转移效应，包括减少活细胞数，抑制迁移，侵袭和粘附，并降低基质金属蛋白酶对人前列腺DU 145癌细胞的活性。此外，本研究结果还提供了紫花苜蓿素抗肿瘤转移机制的可能途径。因此，紫花苜蓿素有可能成为一种新型的前列腺癌治疗药物或辅助治疗药物。
Casticin, a polymethoxyflavone derived from natural plants, has biological activities including induction of cell apoptosis. In this study, we showed the beneficial effects of casticin on the inhibition of prostate cancer cell metastasis. Casticin reduced total viable cell number, thus, we selected low doses of casticin for following experiments. Casticin decreased cell mobility, suppressed cell migration and invasion, and reduced cell gelatinolytic activities of MMP-2/-9. Furthermore, casticin inhibited the protein levels of AKT, GSK3 alpha beta, Snail, and MMPs (MMP-2, -9, -13, and -7) at 24 and 48 hr treatment. Casticin diminished the expressions of NF-kappa B p65, GRB2, SOS-1, MEK, p-ERK1/2, and p-JNK1/2 at 48 hr treatment only. However, casticin reduced the level of E-cadherin at 24 hr treatment but elevated at 48 hr. The novel findings suggest that casticin may represent a new and promising therapeutic agent for the metastatic prostate cancer. Practical applications Casticin derived from natural plants had been used for Chinese medicine in Chinese population for thousands of years. In the present study, casticin attenuated metastatic effects, including decreasing viable cell number, inhibiting the migration, invasion, and adhesion, and reducing matrix metalloproteinases activity on human prostate DU 145 cancer cells. In addition, the results also provided possible pathways involved in casticin anti-metastasis mechanism. We conclude that casticin may be an aptitude anticancer agent or adjuvant for the metastatic prostate cancer in the future.